The present invention is related to determining cardiac performance in a patient. More specifically, the present invention is related to determining cardiac performance in a patient with a conductance catheter which can be excited with multiple frequencies.
Although there are other methods to measure ventricular volumes such as MRI and nuclear technologies, they cannot do so instantaneously. Echocardiography can generate an estimate of instantaneous volume using the modified Simpsons rule or xe2x80x9cstack of discsxe2x80x9d. Because it utilizes a single tomographic plane to estimate three dimensional volumes, it has limitations when applied to patients with regional wall motion abnormalities. Therefore, only improvements in conductance technology offer the ability to make these precise mechanical measurements.
One conductance apparatus commercially available is the Cardiac Function Analyzer made by CardioDynamics in the Netherlands. This apparatus includes the Leycom Sigma 5, a device which is used to measure instantaneous volume from a conductance catheter. The Leycom Sigma 5 has been able to generate adequate volume data in ventricular chambers of large animals which are smaller than 150 ml. However, in patients with congestive heart failure, hearts may range from 180 to 500 ml. It has been previously shown (Reprint 1) that the Sigma 5 cannot generate a homogeneous electric field for volumes seen in human heart failure. Furthermore, there is no built in mechanism for the Sigma 5 to correct for current leakage into the surrounding conductive structures such as myocardium. As a result, it significantly underestimates the stroke volume (volume of blood pumped by the failing heart) and overestimates end-systolic and end-diastolic volumes. In reprints 2-5, there was an average 2-fold underestimation of the stroke volume. U.S. Patent to Carlson teaches that parallel conductance (current leakage outside the blood volume i.e., heart muscle) will be constant at different frequencies, so that this term can be excluded (see column 4, item (6)). Gwane et al. J Appl Physiology vol 63, pg 872-876, 1987 teaches that parallel conductance does vary with frequency, while By stroke volume is constant. The present invention is based on the discovery that since muscle resistivity does vary with frequency and blood does not, the resistivity ratio of blood and muscle will vary with frequency. Hence, both the field density within the left ventricle and the current leakage to the surrounding heart muscle both vary with frequency. The end result is both stroke volume and parallel conductance varying with frequency, which is in contrast to both the Carlson patent and Gwane paper. The apparatus uses a digitally controlled signal synthesizer to drive any conductance catheter. This results in more consistent control over waveform shape, amplitude, and frequency than known before. The use of the digital synthesizer also allows the user to select any type of waveform over a broad range of frequencies to apply to a conductance catheter. The digital signal synthesizer is a Signametrics Complex DDS Generator. The device can couple with commercially available conductance catheters made by numerous vendors. One includes Millar Instruments in Houston, Tex. They market conductance catheters with an incorporated Mikrotip pressure transducer for small animals including transgenic mice (SPR 719) and humans (SPC 550, 560, and 570).
The ability to delete single genes from small animals (mice and rats) to generate transgenic animals is now possible. This allows the study of the effect of a single gene deletion on the development on congestive heart failure (weak heart muscle) and hypertrophy (thickened heart muscle). Investigators are currently utilizing left ventricular pressure or its first derivative (dP/dt); or dimension and fractional shortening (derived by echocardiography). The problem with these isolated pressure and dimension measurements is that they are altered just by the heart size changes which accompany congestive heart failure and hypertrophy. Conductance catheter pressure-volume measurements miniaturized for the transgenic mouse allows the physiologic endpoint of how weak the heart muscle has become to be accurately determined. See xe2x80x9cCardiac physiology in transgenic micexe2x80x9d by James et al., and another paper demonstrating the technique of conductance PV loops in the mouse (Georgakopoulos et al. Am J Physiology 1998), both of which are incorporated by reference herein.
Conductance measurement offers a method to generate an instantaneous left ventricular volume signal in the mouse (Georgakopoulos D, Mitzner W A, Chen C H, Byrne B J, Millar H D, Hare J M, Kass D A. In vivo murine left ventricular pressure-volume relations by miniaturized conductance micromanometry. Am J Physiol 274 (Heart Circ Physiol 43): H1416-H1422, 1998, incorporated by reference herein). It uses an electric field generated from electrodes at the apex and immediately above the left ventricle to sense the instantaneous conductance change as the left ventricle fills and ejects blood. A signal proportional to the left ventricular blood volume is required for use in physiologic studies. Unfortunately, the presently available instantaneous conductance output is a combination of blood and left ventricular muscle (Boltwood C M, Appleyard R F, Glantz S A. Left ventricular volume measurement by conductance catheter in intact dogs: parallel conductance volume depends on left ventricular size. Circulation 80: 1360-1377, 1989; Burkhoff D, Van Der Velde E, Kass D, Baan J, Maughan W L, Sagawa K. Accuracy of volume measurement by conductance catheter in isolated, ejecting canine hearts. Circulation 72: 440-447, 1985; Cabreriza S E, Dean D A, Jia C X, Dickstein M L, Spotnitz H M. Electrical isolation of the heart: stabilizing parallel conductance of left ventricular volume measurement. ASAIO Journal 43: M 509-M 514, 1997; Lankford E B, Kass D A, Maughan W L, Shoukas A A. Does parallel conductance vary during a cardiac cycle? Am J Physiol 258 (Heart Circ Physiol 27): H1933-H1942, 1990; Szwarc R S, Mickleborough L L, Mizuno S I, Wilson G J, Liu P, Mohamed S. Conductance catheter measurements of left ventricular volume in the intact dog: parallel conductance is independent of left ventricular size. Cardiovas Res 28: 252-258, 1994, all of which are incorporated by reference herein). By developing a conductance system that operates at several simultaneous frequencies, identification and possibly correction for the myocardial contribution to the instantaneous volume signal can be had.
This is based on the assumption that patient myocardial conductivity will vary with frequency, while patient blood conductivity will not. Prior work has shown that blood has constant electrical resistivity over a wide range of frequencies (2 to 100 kHz, 22). In contrast, the resistivity of myocardium is known to change with frequency; specifically, the resistivity of myocardium is lower at increased excitation frequency (Epstein B R, Foster K R. Anisotropy in the dielectric properties of skeletal muscle. Med Biol Eng Comput 21: 51-55, 1983; Schwan H P, Kay C F. Specific resistance of body tissues. Circ Res IV: 664-670, 1956; Steendijk P, Mur G, Van Der Velde E, Baan J. The four-electrode resistivity technique in anisotropic media: theoretical analysis and application on myocardial tissue in vivo. IEEE Trans Bio Med Eng 40: 1138-1148, 1993; Steendijk P, Mur G, Van Der Velde E, Baan J. Dependence of anisotropic myocardium electrical resistivity on cardiac phase and excitation frequency. Basic Res Cardiol 89: 411-426, 1994; Zheng E, Shao S, Webster J G. Impedance of skeletal muscle from 1 Hz to 1 MHz. IEEE Trans Biomed Eng 31: 477-483, 1984, all of which are incorporated by reference herein). See FIG. 1. At lower frequencies, there is a maximal gradient between the resistivity of blood and myocardium such that the electric field generated will be primarily confined to the left ventricular cavity and to a lesser degree in the myocardium. At higher frequencies, there will be a minimal gradient between the resistivity of blood and myocardium and the electric field generated will not be confined to the left ventricular cavity but extend into the myocardium. Accordingly, the higher the excitation frequency, the greater the apparent end-diastolic and end-systolic conductance detected by the miniaturized conductance catheter. In addition, if this construct is correct there should be a slight reduction in the difference between end-diastolic and end-systolic conductance at higher frequencies since the relative proportion of the signal changing from systole to diastole is smaller.
This approach could have an important advantage over the traditional conductance method for determining measures of ventricular function such as end-systolic elastance. Since elastance is generated during beat-by-beat changes in loading conditions, a method to determine and correct for instantaneous parallel conductance is critical and does not exist. The use of multiple simultaneous frequencies has the potential to solve this problem. The application of this approach would be in transgenic mice. There is need to relate specific gene products to phenotype. Unfortunately, the ability to rigorously assess the cardiovascular phenotype in very small animals has lagged (Christensen G, Wang Y, Chien K. Physiologic assessment of complex cardiac phenotypes in genetically engineered mice. Am J Physiol 272 (Heart Circ Physiol 41): H 2513-H 2524, 1997, James J F, Hewett T E, Robbins J. Cardiac physiology in transgenic mice. Circ Res 82: 407-415, 1998, both of which are incorporated by reference herein). Such analysis has been available in larger animals by measurement of simultaneous left ventricular pressure and volume to examine cardiac performance in the pressure-volume plane (Baan J, Van Der Velde E T, De Bruin H G, Smeenk G J, Van Dijk A D, Temmerman D, Senden J, Buis B. Continuous measurement of left ventricular volume in animals and humans by conductance catheter. Circulation 70: 812-823, 1984; Kass D A, Yamazaki T, Burkhoff D, Maughan W L, Sagawa K. Determination of left ventricular end-systolic pressure-volume relationships by the conductance (volume) catheter technique. Circulation 73: 586-595, 1986, both of which are incorporated by reference herein). The application of this approach to mice has been difficult due to the small size of the mouse heart and the rapid heart rate. Creating technology to generate an accurate instantaneous volume signal in the transgenic mouse to generate pressure-volume relationships during occlusion of the inferior vena cava is a goal of this study.
By combining experimental data with an analytical approach consisting of a series of equations it was possible to extract an accurate estimate of left ventricular blood and myocardial components.
The present invention pertains to an apparatus for determining cardiac performance in a patient. The apparatus comprises a multifrequency conductance catheter for measuring instantaneous volume of a heart chamber with multifrequencies. The apparatus comprises a mechanism for measuring instantaneous pressure of the heart chamber. The apparatus comprises a mechanism for separating the multifrequencies. The apparatus comprises a mechanism for signal processing the instantaneous volume and the pressure of the heart chamber to identify mechanical strength of the chamber and for automatically producing a plurality of desired waveforms at desired frequencies for the conductance catheter. The processing mechanism is connected to the pressure measuring mechanism, the separating mechanism and the volume measuring mechanism.
At The present invention pertains to a method for determining cardiac performance in a patient. The method comprises the steps of inserting a conductance catheter into an in vivo heart. Next there is the step of sending simultaneously a combined signal consisting of at least two frequencies from a signal source into an amplifier. Then there is the step of applying a current to outer electrodes of the conductance catheter. Next there is the step of measuring an instantaneous voltage signal from the heart with intermediate electrodes of the conductance catheter. Then there is the step of extracting from the intermediate electrodes the combined signal potential from the combined signal. Next there is the step of separating the frequencies from the combined signal potential. Then there is the step of determining the separate conductance associated with each frequency. Next there is the step of identifying pressure volume loops regarding the heart of the patient.